It is the aim of this project to investigate two aspects of IL-1 physiology; 1) whether treatment of cells with agents which alter DNA methylation results in the activation of Il-1 gene expression and 2) what molecular events occur upon IL-1 treatment of an IL-1 sensitive mouse thymocyte cell line. We have found that production of IL-1 by a human monocytic tumor cell lilne, THP-1, can be increased 50% by treatment of the cells with 5-azacytidine and that another human monocytic tumor cell line, U937, can be induced to produce IL-1 following LPS stimulation after a similar treatment with 5-azacytidine. Treatment of either cell line with another agent which affects DNA structure, bromodeoxyuridine, did not result in activation of IL-1 production. We have also found that IL-1 treatment of a sensitive mouse thymocyte cell line, D10G4.1, results in increased expression of the c-myc proto-oncogene as well as both IL-2 mRNA and IL-2 receptor mRNA. Additional studies are currently underway to determine if the expression of other genes such as IFN-Gamma and the fos oncogene, are also altered by IL-1 treatment of these target cells.